Abstract

Attention-deficit/hyperactivity disorder (ADHD) is accompanied by impairments in cognitive control, such as task-switching deficits. We investigated whether such problems, and their remediation by medication, reflect abnormal reward motivation and associated striatal dopamine transmission in ADHD. We used functional genetic neuroimaging to assess the effects of dopaminergic medication and reward motivation on task-switching and striatal BOLD signal in 23 adults with ADHD, ON and OFF methylphenidate, and 26 healthy controls. Critically, we took into account interindividual variability in striatal dopamine by exploiting a common genetic polymorphism (3'-UTR VNTR) in the DAT1 gene coding for the dopamine transporter. The results showed a highly significant group by genotype interaction in the striatum. This was because a subgroup of patients with ADHD showed markedly exaggerated effects of reward on the striatal BOLD signal during task-switching when they were OFF their dopaminergic medication. Specifically, patients carrying the 9R allele showed a greater striatal signal than healthy controls carrying this allele, whereas no effect of diagnosis was observed in 10R homozygotes. Aberrant striatal responses were normalized when 9R-carrying patients with ADHD were ON medication. These pilot data indicate an important role for aberrant reward motivation, striatal dopamine and interindividual genetic differences in cognitive processes in adult ADHD.

Task-switching paradigm with reward manipulation. Participants were instructed to respond either to the direction indicated by the arrow (i.e. ← or →) or to the direction indicated by the word (i.e. ‘left’ or ‘right’) with a left or a right button press. The task performed on a particular trial either changed compared with the preceding trial (i.e. switch trial; arrow–word or word–arrow) or remained the same (i.e. repeat trial; arrow–arrow, word–word). In addition, we manipulated the amount of anticipated reward (e.g. 1 vs. 15 cents) on a trial-by-trial basis by means of a reward anticipation cue. At the start of each trial, this cue indicated the amount of reward on that trial, providing a correct and sufficiently fast button press (see also ).

Rewarded task-switching as a function of the DAT1 genotype in patients with attention-deficit/hyperactivity disorder (ADHD) ON and OFF their methylphenidate medication, relative to healthy controls (HC). (a-I) Increased dorsal striatal responses during rewarded task-switching for patients with ADHD OFF methylphenidate relative to healthy controls, as a function of the DAT1 genotype; (a-II) Increased dorsal striatal responses during rewarded task-switching for patients with ADHD OFF methylphenidate relative to when ON methylphenidate, as a function of the DAT1 genotype; (b) The β values from the whole-brain cluster-corrected cluster in the left striatum depicted in (a-I), showing the direction of the effect; (c) The response times during rewarded task-switching. Positive values reflect an increased switch cost (i.e. slower on switch than on repeat trials) for high reward relative to low reward trials, that is a detrimental effect of reward on the switch cost. Error bars represent the SE of the difference between high reward (switch-repeat) minus low reward (switch-repeat).